Methotrexate as a corticosteroid-sparing agent in leprosy reactions: A French multicenter retrospective study.

INTRODUCTION: Leprosy reactions (LRs) are inflammatory responses observed in 30%-50% of people with leprosy. First-line treatment is glucocorticoids (GCs), often administered at high doses with prolonged courses, resulting in high morbi-mortality. Methotrexate (MTX) is an immunomodulating agent used to treat inflammatory diseases and has an excellent safety profile and worldwide availability. In this study, we describe the efficacy, GCs-sparing effect and safety of MTX in LRs. METHODS: We conducted a retrospective multicentric study in France consisting of leprosy patients receiving MTX for a reversal reaction (RR) and/or erythema nodosum leprosum (ENL) since 2016. The primary endpoint was the rate of good response (GR) defined as the complete disappearance of inflammatory cutaneous or neurological symptoms without recurrence during MTX treatment. The secondary endpoint was the GCs-sparing effect, safety and clinical relapse after MTX discontinuation. RESULTS: Our study included 13 patients with LRs (8 men, 5 women): 6 had ENL and 7 had RR. All patients had had at least one previous course of GCs and 2 previous treatment lines before starting MTX. Overall, 8/13 (61.5%) patients had GR, allowing for GCs-sparing and even GCs withdrawal in 6/11 (54.5%). No severe adverse effects were observed. Relapse after MTX discontinuation was substantial (42%): the median relapse time was 5.5 months (range 3-14) after stopping treatment. CONCLUSION: MTX seems to be an effective alternative treatment in LRs, allowing for GCs-sparing with a good safety profile. Furthermore, early introduction during LRs may lead to a better therapeutic response. However, its efficacy seems to suggest prolonged therapy to prevent recurrence.

Epidemiology and Genetic Variability of HHV-8/KSHV among Rural Populations and Kaposi's Sarcoma Patients in Gabon, Central Africa. Review of the Geographical Distribution of HHV-8 K1 Genotypes in Africa.

Human herpesvirus 8 (HHV-8) is the etiological agent of all forms of Kaposi's sarcoma (KS). K1 gene studies have identified five major molecular genotypes with geographical clustering. This study described the epidemiology of HHV-8 and its molecular diversity in Gabon among Bantu and Pygmy adult rural populations and KS patients. Plasma antibodies against latency-associated nuclear antigens (LANA) were searched by indirect immunofluorescence. Buffy coat DNA samples were subjected to polymerase chain reaction (PCR) to obtain a K1 gene fragment. We studied 1020 persons; 91% were Bantus and 9% Pygmies. HHV-8 seroprevalence was 48.3% and 36.5% at the 1:40 and 1:160 dilution thresholds, respectively, although the seroprevalence of HHV-8 is probably higher in Gabon. These seroprevalences did not differ by sex, age, ethnicity or province. The detection rate of HHV-8 K1 sequence was 2.6% by PCR. Most of the 31 HHV-8 strains belonged to the B genotype (24), while the remaining clustered within the A5 subgroup (6) and one belonged to the F genotype. Additionally, we reviewed the K1 molecular diversity of published HHV-8 strains in Africa. This study demonstrated a high seroprevalence of HHV-8 in rural adult populations in Gabon and the presence of genetically diverse strains with B, A and also F genotypes.

Case Report: A New Gain-of-Function Mutation of STAT1 Identified in a Patient With Chronic Mucocutaneous Candidiasis and Rosacea-Like Demodicosis: An Emerging Association.

Purpose: Heterozygous missense STAT1 mutations leading to a gain of function (GOF) are the most frequent genetic cause of chronic mucocutaneous candidiasis (CMC). We describe the case of a patient presenting a new GOF mutation of STAT1 with the clinical symptoms of CMC, recurrent pneumonia, and persistent central erythema with papulopustules with ocular involvement related to rosacea-like demodicosis. Methods: Genetic analysis via targeted next-generation sequencing (NGS; NGS panel DIPAI v.1) exploring the 98 genes most frequently involved in primary immunodeficiencies, including STAT1, was performed to identify an underlying genetic defect. Results: NGS identified a novel variant of STAT1, c.884C>A (exon 10), p.T295Y, not previously described. This variant was found to be gain of function using an in vitro luciferase reporter assay. Rosacea-like demodicosis was confirmed by substantial Demodex proliferation observed via the microscopic examination of a cutaneous sample. A review of literature retrieved 20 other cases of STAT1 GOF mutations associated with early-onset rosacea-like demodicosis, most with ocular involvement. Conclusion: We describe a new STAT1 GOF mutation associated with a phenotype of CMC and rosacea-like demodicosis. Rosacea-like demodicosis appears as a novel and important clinical phenotype among patients with STAT1 GOF mutation.

Ivermectin versus benzyl benzoate applied once or twice to treat human scabies in Dakar, Senegal: a randomized controlled trial.

OBJECTIVE: To compare the effectiveness of oral ivermectin (IV) and two different modalities of topical benzyl benzoate (BB) for treating scabies in a community setting. METHODS: The trial included patients aged 5-65 years with scabies who attended the dermatology department at the Institut d'Hygiène Sociale in Dakar, Senegal. The randomized, open trial considered three treatments: a single application of 12.5% BB over 24 hours (BB1 group), two applications of BB, each over 24 hours (BB2 group), and oral IV, 150-200 microg/kg (IV group). The primary endpoint was the disappearance of skin lesions and itching at day 14. If necessary, treatment was repeated and patients were evaluated until cured. Results were analysed on an intention-to-treat basis. A pre-planned intermediate analysis was carried out after the BB1, BB2 and IV groups had recruited 68, 48 and 65 patients, respectively. FINDINGS: At day 14, 33 patients (68.8%) in the BB2 group were cured versus 37 (54.4%) in the BB1 group and 16 (24.6%) in the IV group (P < 10-6). Bacterial superinfection occurred more often in the IV group than in the BB1 and BB2 groups combined (28% versus 7.8%, respectively; P = 0.006). At day 28, 46 patients (95.8%) in the BB2 group were cured versus 52 (76.5%) in the BB1 group and 28 (43.1%) in the IV group (P < 10-5). These clear findings prompted early study cessation. CONCLUSION: Topical BB was clearly more effective than oral IV for treating scabies in a Senegalese community.

Prevalence and genetic diversity of hepatitis B and delta viruses in pregnant women in Gabon: molecular evidence that hepatitis delta virus clade 8 originates from and is endemic in central Africa.

Hepatitis B virus (HBV) surface antigen (HBsAg) was found in 9.2% of 1,186 pregnant women from Gabon, of whom 10.1% had the HBe antigen and 89.9% had anti-HBe antibodies. Antibodies to the hepatitis delta virus (HDV) were found in 15.6% of the HBsAg-positive women. The HBV strains were of the A3 and E genotypes. The HDV strains belonged to HDV clades 1 and 8. These results provide clear evidence that HDV clade 8 is indigenous to Africa.

New insights into prevalence, genetic diversity, and proviral load of human T-cell leukemia virus types 1 and 2 in pregnant women in Gabon in equatorial central Africa.

Human T-cell leukemia virus type 1 (HTLV-1) is highly endemic in areas of central Africa; mother-to-child transmission and sexual transmission are considered to be the predominant routes. To determine the prevalence and subtypes of HTLV-1/2 in pregnant women in Gabon, we conducted an epidemiological survey in the five main cities of the country. In 907 samples, the HTLV-1 seroprevalence was 2.1%, which is lower than that previously reported. Only one case of HTLV-2 infection was found. The HTLV-1 seroprevalence increased with age and differed between regions (P

Hepatitis C virus prevalence and genetic diversity among pregnant women in Gabon, central Africa.

BACKGROUND: Hepatitis C virus (HCV) infection is a major global public health problem in both developed and developing countries. The prevalence and genetic diversity of HCV in pregnant women in Gabon, central Africa, is not known. We therefore evaluated the prevalence and the circulating genotypes of HCV in a large population cohort of pregnant women. METHODS: Blood samples (947) were collected from pregnant women in the five main cities of the country. The prevalence was evaluated by two ELISA tests, and the circulating genotypes were characterized by sequencing and phylogenetic analysis. RESULTS: Twenty pregnant women (2.1%) were infected with HCV. The seroprevalence differed significantly by region (p = 0.004) and increased significantly with age (p = 0.05), being 1.3% at 14-20 years, 1.1% at 21-25 years, 1.9% at 26-30 years, 4.1% at 31-35 years and 6.0% at > 35 years. Sequencing in the 5'-UTR and NS5B regions showed that the circulating strains belonged to genotypes 4 (4e and 4c). CONCLUSION: We found that the HCV seroprevalence in pregnant women in Gabon is almost as high as that in other African countries and increases with age. Furthermore, only genotype 4 (4e and 4c) was found. More extensive studies aiming to evaluate the prevalence and heterogeneity of HCV genotypes circulating in the general population of the country are needed.

A Teledermatology Pilot Programme for the Management of Skin Diseases in Primary Health Care Centres: Experiences from a Resource-Limited Country (Mali, West Africa).

In sub-Saharan Africa, in particular in rural areas, patients have limited access to doctors with specialist skills in skin diseases. To address this issue, a teledermatology pilot programme focused on primary health centres was set up in Mali. This study was aimed at investigating the feasibility of this programme and its impact on the management of skin diseases. The programme was based on the store-and-forward model. Health care providers from 10 primary centres were trained to manage common skin diseases, to capture images of skin lesions, and to use an e-platform to post all cases beyond their expertise for dermatologists in order to obtain diagnosis and treatment recommendations. After training, the cases of 180 patients were posted by trained health workers on the platform. Ninety-six per cent of these patients were properly managed via the responses given by dermatologists. The mean time to receive the expert's response was 32 h (range: 13 min to 20 days). Analysis of all diseases diagnosed via the platform revealed a wide range of skin disorders. Our initiative hugely improved the management of all skin diseases in the targeted health centres. In developing countries, Internet accessibility and connection quality represent the main challenges when conducting teledermatology programmes.

[Leprosy is definitely not a disease of the past]. / La lèpre n'est pas une maladie du passé.

In this review we present a synthesis of the current knowledge of leprosy based on the epidemiological studies and the latest data obtained in basic research and the strategies undertaken to fight out this pathology. The significant progress in the genomic study of the leprosy bacillus, and in understanding the basic mechanisms governing the individual susceptibility to the disease, together with the stagnation in the incidence of the new cases observed for ten years, represent focus of interest. If the efficiency of the recommended treatments is actually confirmed by a low relapse rate, however the drying up of new cases, which could be expected by reducing the infectiousness of the treated cases, is nonetheless slow in coming. Recent studies support the effectiveness of prophylaxis based on a single dose of rifampicin and/or a BCG vaccination of patient contacts. This could allow an increased reduction of the incidence of the disease. However, no official position validates such strategies. Because of an ambiguity in the expression of the objectives for managing the disease, i.e. « elimination of a disease considered as a public health problem ¼, which should not to be confused with « eradication of the disease ¼, which, in fact, has no relevance today, demobilization in fighting against leprosy is to be feared.

18F-FDG PET/CT Findings in a Patient With a Proliferating Trichilemmal Cyst.

Proliferating trichilemmal cyst is considered as a rare tumor that originates in the outer root sheath of hair follicle. Metastatic potential has not been yet fully established. Moreover, histological analysis does not allow precise malignancy prediction. Proliferating trichilemmal cyst glucose metabolism behavior was never previously described. Herein, we report the case of a 62-year-old patient with a left shoulder proliferating trichilemmal cyst showing an intense uptake of ¹8F-FDG on PET/CT examination. ¹8F-FDG PET/CT could be proposed to optimize diagnostic strategy of patients with proliferating trichilemmal cysts.

The Global Epidemiology of Impetigo: A Systematic Review of the Population Prevalence of Impetigo and Pyoderma.

OBJECTIVE: We conducted a comprehensive, systematic review of the global childhood population prevalence of impetigo and the broader condition pyoderma. METHODS: PubMed was systematically searched for impetigo or pyoderma studies published between January 1 1970 and September 30 2014. Two independent reviewers extracted data from each relevant article on the prevalence of impetigo. FINDINGS: Sixty-six articles relating to 89 studies met our inclusion criteria. Based on population surveillance, 82 studies included data on 145,028 children assessed for pyoderma or impetigo. Median childhood prevalence was 12·3% (IQR 4·2-19·4%). Fifty-eight (65%) studies were from low or low-middle income countries, where median childhood prevalences were 8·4% (IQR 4·2-16·1%) and 14·5% (IQR 8·3-20·9%), respectively. However, the highest burden was seen in underprivileged children from marginalised communities of high-income countries; median prevalence 19·4%, (IQR 3·9-43·3%). CONCLUSION: Based on data from studies published since 2000 from low and low-middle income countries, we estimate the global population of children suffering from impetigo at any one time to be in excess of 162 million, predominantly in tropical, resource-poor contexts. Impetigo is an under-recognised disease and in conjunction with scabies, comprises a major childhood dermatological condition with potential lifelong consequences if untreated.

Drug Hypersensitivity Syndrome in a West-Indian population.

Some studies have suggested an ethnic susceptibility to Hypersensitivity Syndrome. We did a 7-year-prospective study in Guadeloupe whose population is mainly of African ancestry, and has free access to modern care facilities. Most patients included were Afro-Caribbeans (26/28), and females (20/28). However, ethnic distribution did not reach significant conclusions. Annual incidence rate was estimated at 0.9/100,000. Medium incubation and duration were 33 and 66 days respectively. Two patients with grade 4 hepatitis died from the syndrome. Two thirds of the patients were given prednisone, which usually alleviated the systemic symptoms, but did not prevent their development (in 5 patients) nor death. Carbamazepine, allopurinol, and minocycline accounted for 2/3 of the cases. Sixty four percent of the causative prescriptions were judged inappropriate. DHS appeared as the most frequent type of severe systemic drug reaction in this population, and may largely be prevented by rational prescribing.

The practice of skin-bleaching for a cosmetic purpose in immigrant communities.

BACKGROUND: Using skin-lightening compounds for a cosmetic purpose that are normally restricted to medical use or forbidden has become a world-wide practice. Complications are numerous. Immigrant communities often import their practice from their original country. METHODS: A review of the literature on the subject of complications of cosmetic skin-bleaching, with special focus on data concerning immigrants originating from highly endemic countries, was conducted. RESULTS: Complications of cosmetic skin-bleaching are common, involving mainly the skin although some general complications are also reported with a growing incidence. CONCLUSION: The high frequency of this practice, added to the frequency of various complications, suggests it might be considered as a genuine public health problem currently.